Rod shaped apatite crystals having a specific length-to-width ratio

ABSTRACT

The rod-shaped apatite crystals of the formula Ca 5 (PO 4 ) 3 (OH) x F y  have the following features a) the length-to-breadth ratio of the crystals is at least ≧5 and b) x+y=1, where if x or y≠0 the total amount of the crystals is present as a mixture of individual hydroxyapatite crystals and fluoroapatite crystals and/or as mixed crystals, such that, based on the total amount of the crystals, (1−x)·100% of the hydroxide ions present if y=0 are replaced by fluoride ions. The invention furthermore describes dispersions which contain such rod-shaped apatite crystals, and a process for the preparation of the dispersions or of the apatite crystals.

The invention relates to rod-shaped apatite crystals which have alength-to-breadth ratio of ≧5 and in which the ratio of hydroxide ionsto fluoride ions based on the total amount of the crystals can be simplyvaried. Furthermore, the invention relates to dispersions which containsuch rod-shaped apatite crystals, and to a process for the preparationof the dispersions or of the apatite crystals.

The dental enamel, just like human bone, consists mainly ofhydroxyapatite. Owing to mechanical stress on the teeth (e.g. wheneating or else alternatively when brushing the teeth), fissures andchannels result in the dental enamel, which expose pores in the interiorof the tooth. Substances can rapidly penetrate into the interior of thetooth through these pores and irritate the dental nerve, as a result ofwhich the teeth become sensitive to sweetness, heat or cold. Moreover,in the case of bacterial attack caries forms in the fissures or in thepores, which is known extensively as a very dangerous dental disease.

This problem has been known for a relatively long time and accordinglythere are innumerable toothpastes or tooth gels which treat the poreformation in different ways. Particulate dispersed calcium phosphatecrystals (having diameters of >5 μm) are frequently employed as calciumand phosphate ion suppliers for the construction of hydroxyapatite, as aresult of which the fissures and unevenness of the tooth surface shouldbe made good again. Most frequently, however, fluoride-containingcompounds such as calcium fluoride are employed, as the conversion ofthe hydroxyapatite of the dental enamel into the significantly harderfluoroapatite is promoted by fluoridation. Fluoroapatite is lesssusceptible to bacterial attack and attacks by proteins than purehydroxyapatite. Consequently, the dental enamel is strengthened andsmoothed by fluoroapatite and the pores in the interior of the tooth arebetter sealed. Furthermore, there are also toothpastes which alreadycontain hydroxyapatite (crystals) and/or fluoroapatite (crystals).Generally, however, fluorides cannot be added in any desired greatamount, since in free form they discolor the teeth from a certainconcentration.

It is furthermore known that flat, in particular rod-shaped,hydroxyapatite crystals adsorb better on the tooth surface and form asheet structure by self-organization which can seal the fissures andpores over a wide area. Rod-shaped crystals therefore have a betteradsorbability, since the underlying van-der-Waal's interactions areproportional to the (surface) area. After the application, a mineralprotective film thereby forms rapidly on the teeth, which in the courseof time becomes identical to dental enamel by means of slow dissolutionin the oral cavity and adsorption of the fluoride-containing compoundslikewise contained in the toothpastes, smooths the dental enamel andeffectively seals the fissures and/or pores.

A problem, however, is the provision of rod-shaped (hydroxy)apatitecrystals which make possible an effective adsorption on the toothsurface on account of an improved length-to-breadth ratio. The processesknown hitherto for the preparation of apatite crystals usually yieldcrystals of spherical and irregular shape having particle sizes of >5μm. In the recent past, however, processes have been published withwhich, in addition to the irregular and spherical shapes, rod-shapedapatite crystals having particle sizes in the submicrometer range canalso be produced.

WO 00/37033 describes suspensions of only slightly water-soluble calciumphosphates, calcium fluorides and calcium fluorophosphates, and theiruse in dental care compositions. The calcium salts contained in thesuspensions are prepared by precipitation in an alkaline medium, thecalcium salts being obtained in the form of crystals (primary particles)having thicknesses (diameters) of 0.005 to 0.05 μm and lengths of 0.01to 0.15 μm. In order to stabilize the suspensions, the precipitation ofthe calcium salts is carried out in the presence of agglomerationinhibitors, such as water-soluble surfactants or water-soluble polymericprotective colloids. In this manner, suspensions of hydroxyapatitecrystals and fluorine-doped hydroxyapatite crystals can also beprepared. The calcium salt crystals prepared in this way in some caseshave rod-shaped structures. Inherent in the method, however, is thedisadvantage that on account of the overlapping length and breadthvalues of the crystals a numerically large amount of crystals is alsoproduced whose length-to-breadth ratio is in the range from 1 to 2, i.e.these crystals have no pronounced rod form or only a slightly pronouncedrod form.

In WO 01/01930, composite materials are described which comprise calciumsalts which are poorly soluble in water, such as calcium phosphates andcalcium fluorophosphates, and a protein component. The calcium salts,which also include hydroxyapatite, fluoroapatite and fluorine-dopedhydroxyapatite, are prepared by precipitating them in the alkalinemedium in the presence of the protein component. Optionally, the calciumsalts (at least partially) also have rod-shaped structures, anumerically large amount of crystals having a length-to-breadth ratio of1 to 2 resulting on account of the likewise overlapping length andbreadth values of the calcium salt crystals prepared using this method.The crystals are deposited on the surface of the high molecular weightprotein component employed, as a result of which they represent thespatial structure of the protein component to a certain extent. Thesecomposite materials can be used for “biomineralization” (mineralcrystallization in a protein matrix), i.e. protein and calcium saltcrystals are incorporated into the protein matrix of the teeth or bone.Consequently, the 3-dimensional structure of the composite materials isapplied to the previous (tooth) surface, while, as mentioned above,hydroxyapatite crystals form laminar, 2-dimensional layers on the(tooth) surface. The biomineralization process, however, iscomparatively slow and leads to composite materials applied to the(tooth) surface whose mechanical properties can differ considerably fromthose of the pure crystals.

WO 98/18719 describes a process for the lengthening of rod-shapedhydroxyapatite crystals in suspensions and the adjustment orconcentration of the solids content of hydroxyapatite crystals in thesesuspensions. By means of alternate stirring and filtering off at definedtime intervals and using defined stirrer speeds, on the one hand theoriginal crystal length of 0.05 to 0.1 μm can be increased to 0.1 to 0.5μm with constant breadth of 0.01 to 0.02 μm, on the other hand a solidscontent of 7 to 96% of hydroxyapatite crystals can be established in thesuspension. As a result of the numerous stirring and filtering steps,the process is complicated; moreover, it is exclusively restricted tosuspensions of hydroxyapatite crystals. The crystal length moreover alsoappears to be dependent on the solids content in the suspension.

The object underlying the invention consists in the provision ofrod-shaped apatite crystals which have an improved length-to-breadthratio compared with the prior art, and in which the ratio of hydroxideions to fluoride ions based on the total amount of the crystals can besimply varied. At the same time, suspensions of the rod-shaped apatitecrystals having a variable solids content should also be provided.

The object is achieved by a process for the preparation of dispersionswhich contain the rod-shaped apatite crystals described beforehand. Theprocess according to the invention contains the following steps:

-   a) in an autoclave, a mixture is produced which contains the    starting materials and water,-   b) a temperature of at least 100° C. and a pressure of >1 bar is    generated in the interior of the autoclave and these conditions are    maintained for at least 1 hour,-   c) if appropriate, following step b), at least one    fluoride-containing compound is added to the mixture present as a    dispersion situated in the autoclave and mixed with this dispersion    over a period of time of at least 1 hour.

The pure apatite crystals can be isolated from the dispersions thusobtained by subjecting the dispersions to drying, in particular spraydrying, in an additional process step.

The advantage of the solution according to the invention lies in thefact that a novel process is provided with which apatite crystals can beprepared which are exclusively rod-shaped. Moreover, the process isrestricted not only to the preparation of hydroxyapatite crystals, butmixtures of rod-shaped hydroxyapatite crystals and rod-shapedfluoroapatite crystals or rod-shaped mixed crystals of hydroxyapatiteand fluoroapatite can also be prepared.

The rod-shaped apatite crystals prepared using the process according tothe invention have a length-to-breadth ratio of ≧5. This means that thecrystals have a length-to-breadth ratio of 5 in the “most unfavorable”case, whereas, however, there are also a significant number of crystalswhich have a length-to-breadth ratio of markedly greater than 5, forexample 8 to 15. In most processes according to the prior art, however,as already mentioned beforehand, a numerically large amount of crystalshaving a length-to-breadth ratio of 1 to 2 is produced.

Since all apatite crystals have a length-to-breadth ratio of ≧5, theadsorption on the tooth surface and the self-organization associatedtherewith functions, with formation of laminar structures, significantlybetter than with apatite crystals which have an unfavorablelength-to-breadth ratio, because the apatite crystals according to theinvention can also be packed particularly tightly. This is also anadvantage compared with that prior art in which the apatite crystalsused there are applied to the surface of proteins and are incorporatedinto the tooth or bone material together with these in abiomineralization process. The crystals incorporated by this processcannot be packed so tightly on the tooth surface as those produced bythe process according to the invention. Moreover, the preparation costsof these mixtures of proteins and apatite crystals are much higher thanthe preparation costs of the rod-shaped apatite crystals of the processaccording to the invention, in which no protein component is necessary.

A further advantage of the process according to the invention can beseen in the simple handling of the adjustment of the fluoride ionconcentration. In the first process section, the hydroxyapatite crystalshave already been produced in rod form, in the second process section adefined number of hydroxide ions can be replaced by fluoride ions in anion-exchange process without the rod form of the crystals being modifiedin this process. By means of this process, in which both purefluoroapatite crystals and mixed crystals of fluoroapatite andhydroxyapatite are produced, a total amount of apatite crystals isprepared which contains a defined, freely adjustable amount of fluorideions. This is particularly of importance in the use of the apatitecrystals, since the apatite crystals applied to the tooth surface forthe sealing of holes or fissures form a mineral protective film, whichsolidifies more rapidly due to the incorporation of fluoride ions andthus also becomes identical to dental enamel more rapidly. As a result,the pores and fissures on the tooth surface are particularly effectivelyand rapidly sealed, and the danger of the formation of caries no longerexists at these sites.

The process according to the invention is suitably carried out in anautoclave, in particular a stirred autoclave. Furthermore, other vesselsor devices known to the person skilled in the art can also be used,which withstand the reaction conditions under elevated pressure.

In the first step (a) of the process according to the invention, amixture, for example in the form of a suspension, is produced in theautoclave from the starting materials and water.

Suitable starting materials are, as the calcium-containing component,calcium hydroxide and, as the phosphorus-containing component,phosphoric acid. Optionally, additives such as calcium chloride, calciumnitrate (tetrahydrate), ammonium hydrogenphosphate or diammoniumhydrogenphosphate can also be admixed to the reaction. Calcium hydroxideand phosphoric acid are particularly suitable, the latter is preferablyemployed in 85% strength by weight form. Water is understood in theprocess according to the invention as in particular meaning completelydeionized water, optionally the water, however, can also have a highresidual ion content, for example of hydroxide ions and/or protons.

In a preferred embodiment of the process according to the invention,completely deionized water is introduced into the autoclave and calciumhydroxide is added to the autoclave with stirring at room temperature.The suspension thus obtained is warmed to 40 to 50° C. and thephosphoric acid, which is optionally diluted with completely deionizedwater, is allowed to run into the autoclave with stirring over asuitable period of time.

In the second step (b) of the process according to the invention, whichcan also be regarded as a hydrothermal process, a temperature of atleast 100° C. and a pressure of >1 bar is generated in the interior ofthe autoclave, and these conditions are maintained for at least 1 hour,preferably 5 to 16 hours. Preferably, the second process step is carriedout at pressures between 1.5 and 6 bar, particularly preferably between2 and 5 bar. Preferred temperature ranges are 105° C. to 150° C., and110° C. to 130° C. are particularly preferred. If appropriate,temperature gradients can also be used, temperature changes also causingpressure changes. In a particularly preferred embodiment of the processaccording to the invention, the conditions of the second process stepare maintained for 10 to 14 hours with stirring. If appropriate, thesecond process step can also be carried out in less than 1 hour.

By means of the second process step, dispersions are obtained whichcontain rod-shaped hydroxyapatite crystals and which are preferablyhomogeneous. The solids content of these dispersions is 5 to 70% byweight, preferably 10 to 40% by weight, particularly preferably 15 to30% by weight, of hydroxyapatite crystals; if appropriate, the solidscontent can also be <5% by weight. The hydroxyapatite crystals preparedin this way (nearly always) have a rod-shaped form, thelength-to-breadth ratio of the (individual) crystals being ≧5, butbeing >20 only in exceptional cases. A length-to-breadth ratio of 8 to15 is preferred, particularly preferably of 9 to 12. In particular,rod-shaped hydroxyapatite crystals can be prepared which have a lengthof 0.1 to 0.2 μm and a breadth of 0.01 to 0.02 μm, in each case based onthe individual crystals. In a furthermore preferred embodiment, thethickness (i.e. the 3rd dimension) of the crystals corresponds to theirbreadth. It is thus evident that the crystals prepared by the processaccording to the invention only have a length-to-breadth (or thickness)ratio of 5 in the “most unfavourable” case. This case occurs with acrystal length of 0.1 μm and a crystal breadth or thickness of 0.02 μm.The length-to-breadth ratio can, however, also be at most 20 (length:0.2 μm; breadth: 0.01 μm). The length-to-breadth ratio of the individualcrystals can be controlled by the parameters pressure, temperature andreaction time in the second process step.

The rod-shaped hydroxyapatite crystals can also be isolated from thedispersion. The dispersant can be removed by simple evaporation, ifappropriate with the aid of vacuum. Furthermore, the dispersion can alsobe subjected to freeze drying for the isolation of the apatite crystals.Preferably, the rod-shaped hydroxyapatite crystals prepared using theprocess according to the invention are isolated from the dispersion byspray drying, and the device necessary for this and the carrying out ofthe spray drying are known to the person skilled in the art. Theisolated hydroxyapatite crystals can be redispersed again in waterwithout problems to give homogeneous dispersions. If appropriate,instead of water, organic compounds such as water-soluble, loweralcohols and glycols, polyethylene glycols, glycerol and mixtures of theorganic compounds mentioned beforehand with one another and/or withwater as dispersant can also be used for the redispersion.

In a third process step (c), the hydroxide ions in the hydroxyapatitecrystals prepared according to the invention can be (partially) replacedby fluoride ions. For this, at least one fluoride-containing compound isadded to the dispersion prepared in the second process step. Suitablefluoride-containing compounds are sodium fluoride, calcium fluoride,potassium fluoride and ammonium fluoride, and sodium fluoride ispreferably suitable. The mixture thus obtained is mixed over a period oftime of at least one hour, preferably 10 to 14 hours. Preferably, it isstirred at room temperature, if appropriate higher temperature valuesand/or lower mixing times than 1 hour can also be used. The thirdprocess step is presumably based on an ion-exchange mechanism.

On the basis of the additional third process step, dispersions accordingto the invention comprising rod-shaped apatite crystals of the formulaCa₅(PO₄)₃(OH)_(x)F_(y) can be prepared, where x+y=1. If x or y≠0, thetotal amount of the crystals is present as a mixture of individualhydroxyapatite crystals and fluoroapatite crystals (i.e. in the crystalthe hydroxide ions have been completely replaced by fluoride ions)and/or as mixed crystals of fluoroapatite and hydroxyapatite, where,based on the total amount of the crystals, (1−x)·100% of the hydroxideions present if y=0 are replaced by fluoride ions.

Provided in the third process step fluoride-containing compounds ormixtures of fluoride-containing compounds are employed which contain nocalcium ions as cations or do not exclusively contain calcium ions, thecalcium ions of the rod-shaped apatite crystals can be partiallysubstituted by the cations deriving from the fluoride-containingcompound. In the following text, those rod-shaped apatite crystals inwhich the calcium ions are partially replaced by the cations derivingfrom the fluoride-containing compounds should also be included by theformula Ca₅(PO₄)₃(OH)_(x)F_(y).

As a result of the replacement of the hydroxide ions by fluoride ionsand, if appropriate, as a result of the partial calcium ion replacement,neither the form or size of the apatite crystals nor the solids contentin the dispersion have changed, i.e. the details given with respect tothis for the hydroxyapatite crystals (x=1) also apply for the apatitecrystals of the formula Ca₅(PO₄)₃(OH)_(x)F_(y). It may again beexpressly mentioned that by means of the process according to theinvention rod-shaped apatite crystals of the formulaCa₅(PO₄)₃(OH)_(x)F_(y) can be prepared in which the length-to-breadthratio of the crystals is ≧5, preferably 8 to 15, particularly preferably9 to 12. It is furthermore preferred that the thickness of the crystalscorresponds to their breadth.

Any desired values for y from 0 to 1 can be set; this is controlled bythe amount of the fluoride-containing compounds added, the temperaturevalues and the duration of the mixing process in the third process step.Preferably, rod-shaped apatite crystals are prepared in which, based onthe total amount of the crystals, 0.01 to 30%, particularly preferably0.5 to 20%, of the hydroxide ions present if y=0 are replaced byfluoride ions. The rod-shaped apatite crystals of the formulaCa₅(PO₄)₃(OH)_(x)F_(y) are isolated from the dispersion analogously tothe details for the case where x=1 (hydroxyapatite crystals).

In a further embodiment of the present invention, the rod-shaped apatitecrystals of the formula Ca₅(PO₄)₃(OH)_(x)F_(y) contained in thedispersion can be surrounded by one or more surface-modifying agents.Surface-modifying agents are understood as meaning substances whichadhere physically to the surface of the crystals, but do not reactchemically with these. Surface-modifying agents are particularly to beunderstood as meaning dispersants; the latter are known to the personskilled in the art, for example, also under the terms emulsifiers,protective colloids, wetting agents or detergents. Suitablesurface-modifying agents are described, for example, in WO 01/01930.Furthermore, antiallergics and/or antiinflammatory active compounds canbe used as surface-modifying agents. The surface-modifying agents areapplied to the surface of the rod-shaped apatite crystals following theprocess for the preparation of rod-shaped apatite crystals according tothe invention by processes known to the person skilled in the art.

The apatite crystals of the formula Ca₅(PO₄)₃(OH)_(x)F_(y) preparedusing the process according to the invention are suitable in isolatedform and/or in the form of dispersions for use as a remineralizingcomponent for teeth and/or bone. The apatite crystals can be presentboth in cleansing and care formulations and in formulations for thetreatment of tooth- and bone defects. Tooth gels, toothpastes (or toothcreams), mouthwash (or mouth rinses) and chewing gum may be mentioned inparticular. Furthermore, the apatite crystals according to the presentinvention are used as a constituent of formulations for the induction orpromotion of the new growth of bone tissue and for the coating ofimplants.

The invention is additionally illustrated with the aid of the followingexamples.

EXAMPLE 1

16.0 kg of completely deionized water were introduced into a (stirred)autoclave of volume 55 l. 5.925 kg of calcium hydroxide (Schäfer whitelime hydrate, Precal 54) were added in while stirring with an anchorstirrer at 90 revolutions per minute (rpm) and the suspension resultingtherefrom was heated to 45° C.

5.534 kg of 85% strength phosphoric acid, which was diluted with 10.390kg of completely deionized water, were allowed to run in at thistemperature over the course of 120 min.

The autoclave was then sealed and the temperature was raised to 100° C.After stirring at 100° C. for 20 min, the temperature was raised to 120°C., whereupon a pressure of 2.3 bar was established.

The mixture was stirred under these conditions for 12 h, then cooled toroom temperature.

After cooling, a solids content of 21.6% and a Ca/P ratio of 1.69 wasdetermined for the dispersion thus obtained. A sample of the dispersionwas taken, from which the dispersing agent was then removed by drying at120° C. and about 10 mbar. The dried crystals showed the diffractionreflections of pure hydroxyapatite in the X-ray diffractogram.

The hydroxyapatite obtained consisted of stalk-shaped crystals ofprismatic cross-section with breadths and thicknesses of 0.01 to 0.02 μmand lengths of 0.1 to 0.2 μm. The specific surface area was 49.4 m²/g.

EXAMPLE 2

Example 2 was carried out analogously to example 1. After the dispersioncontaining the hydroxyapatite had been cooled to room temperature, 0.168kg of sodium fluoride was added to the autoclave and the dispersion wasstirred at room temperature for a further 12 h.

The suspension was then drawn off from the autoclave. The X-raydiffractogram of a dried sample showed that about 20 mol % of thehydroxide ions, based on the total amount of the crystals, had beenreplaced by fluoride ions. The form and the dimensions of the crystalshave not changed compared with those of the crystals from example 1. Thespecific surface area was 49.4 m²/g.

EXAMPLE 3

Example 2 was repeated with the difference that after 20 min thereaction-contents were heated at 100° C. to 150° C. and the reactiontime at this temperature was reduced to 4 h. The pressure under theseconditions was 4.5 bar. After the dispersion containing thehydroxyapatite had been cooled to room temperature, 0.067 kg of sodiumfluoride was added.

The X-ray diffractogram of the dried sample showed that about 8 mol % ofthe hydroxide ions based on the total amount of the crystals, had beenreplaced by fluoride ions. The specific surface area was 46.8 m²/g, theCa/P ratio was 1.65, and the shape and the dimensions of the crystalscorresponded to those from example 1.

COMPARISON EXAMPLE C1

16.0 kg of completely deionized water were introduced into a stirredcontainer of volume 55 l and 5.925 kg of calcium hydroxide (Schäferwhite lime hydrate, Precal 54) were added in while stirring with ananchor stirrer at 90 rpm and the suspension resulting therefrom washeated to 70° C.

5.534 kg of 85% strength phosphoric acid, which was diluted with 10.39kg of completely deionized water, were allowed to run in at thistemperature over the course of 30 min while cooling and keeping thetemperature constant.

The reaction mixture was stirred at 70° C. for a further 2 h and thencooled to room temperature.

A solids content of 21.3% was determined for the dispersion thusobtained after cooling. The X-ray diffractograms of the crystals whichwere isolated from the dispersion showed the diffraction reflections ofhydroxyapatite. The hydroxyapatite had the form of irregular sphereshaving diameters of 0.4 to 5 μm.

1-13. (canceled)
 14. Rod-shaped apatite crystals of the formulaCa₅(PO₄)₃(OH)_(x)F_(y), wherein a) the length-to-breadth ratio of thecrystals is ≧5 and b) x+y=1.
 15. Rod-shaped apatite crystals as claimedin claim 14, wherein y≠0 and the calcium ions are partially substitutedby other cations.
 16. Rod-shaped apatite crystals as claimed in claim15, wherein the cations are selected from the group consisting ofsodium, potassium and ammonium ions.
 17. Rod-shaped apatite crystals asclaimed in claim 14, wherein the length-to-breadth ratio of the crystalsis in a range of 5 to
 20. 18. Rod-shaped apatite crystals as claimed inclaim 17, wherein the length-to-breadth ratio of the crystals is in arange of 8 to
 15. 19. Rod-shaped apatite crystals as claimed in claim14, wherein y is in the range of 0.0001 to 0.3.
 20. Rod-shaped apatitecrystals as claimed in claim 14, wherein the thickness and the breadthof the individual crystals are approximately equal.
 21. Rod-shapedapatite crystals as claimed in claim 14, wherein the breadth is 0.01 to0.02 μm and the length of the crystals is 0.1 to 0.2 μm.
 22. Rod-shapedapatite crystals as claimed in claim 21, wherein the thickness and thebreadth are 0.01 to 0.02 μm and the length of the crystals is 0.1 to 0.2μm.
 23. A dispersion comprising rod-shaped apatite crystals as claimedin claim 14, wherein the solids content of apatite crystals is 5 to 70%by weight.
 24. The dispersion as claimed in claim 23, wherein the solidscontent of apatite crystals is 15 to 30% by weight.
 25. A process forthe preparation of dispersions comprising rod-shaped apatite crystals asclaimed in claim 14, which comprises a) producing, in an autoclave, amixture which contains a calcium-containing component, aphosphorous-containing component and water, b) generating a temperatureof at least 100° C. and a pressure of >1 bar in the interior of theautoclave and maintaining these conditions for at least 1 hour, and c)optionally, following step b), adding at least one fluoride-containingcompound to the mixture present as a dispersion situated in theautoclave and mixing with this dispersion over a period of time of atleast 1 hour.
 26. A process as claimed in claim 25, wherein in step b)the temperature is in a range of 105° C. to 150° C.
 27. A process asclaimed in claim 25, wherein the rod-shaped apatite crystals areisolated from the dispersion.
 28. A process as claimed in claim 25,wherein the calcium-containing component is calcium hydroxide and thephosphorous-containing component is phosphoric acid.
 29. A process asclaimed in claim 25, wherein the fluoride-containing compound is atleast one of sodium fluoride, calcium fluoride, potassium fluoride andammonium fluoride.
 30. A process as claimed in claim 25, wherein apressure of between 1.5 and 6 bar is generated in the interior of theautoclave.
 31. A process as claimed in claim 27, wherein the rod-shapedapatite crystals are isolated from the dispersion by spray drying. 32.Rod-shaped apatite crystals as claimed in claim 14, wherein thelength-to-breadth ratio of all of the crystals is ≧5.
 33. Rod-shapedapatite crystals obtainable by a process as claimed in claim
 27. 34.Rod-shaped apatite crystals as claimed in claim 14, which areexclusively rod-shaped.
 35. A mixture containing individual rod-shapedapatite crystals as claimed in claim 14.